Critical flicker frequency test predicts overt hepatic encephalopathy and survival in patients with liver cirrhosis

Background: A critical flicker frequency (CFF) ≤39 Hz identifies cirrhotic patients with minimal hepatic encephalopathy (mHE) and predicts the risk of both overt hepatic encephalopathy (oHE) and mortality in patients with previous episodes of decompensation and/or oHE. Aims: Herein, we evaluated the effectiveness of CFF in predicting the first episode of oHE and survival in cirrhotics who had never experienced an episode of oHE. Methods: Our cohort study of 134 patients and 150 healthy subjects were examined. A CFF > 39 Hz was considered normal and pathological when ≤39 Hz. The median follow up was 36 months. Results: At baseline, all controls had CFF > 39 Hz. Ninety-three patients had a CFF > 39 Hz and 41 had a CFF ≤ 39 Hz. The prevalence of CFF ≤ 39 Hz significantly increased with the progression of the Child-Pugh class (p = 0.003). Moreover, the risk of oHE was increased by CFF ≤ 39 (p < 0.001, by log-rank test) [HR = 7.57; CI(3.27-17.50); p < 0.0001, by Cox model] and ammonia [HR = 1.02 CI(1.01-1.03), p = 0.0009]. Both a CFF value ≤ 39 Hz and Child-Pugh class were independent predictors of mortality by Cox model [HR = 1.97; CI(1.01-3.95), p = 0.049; HR = 3.85 CI(1.68-8.83), p = 0.003]. Conclusions: CFF predicts the first episode of oHE in cirrhotics that had never experienced oHE, and predicts mortality risk. These findings suggest that cirrhotic patients should be routinely screened by CFF.